Abstract

Local drug delivery methods allow for the opportunity to supply potent multispectrum antibiotics such as vancomycin hydrochloride to sites of infection, while avoiding systemic toxicity. In this work, layer-by-layer assembly of polymer multilayer films is applied to create vancomycin delivery coatings. By taking advantage of the versatile layer-by-layer spray and dip coating techniques, thin films were generated based on electrostatic and other secondary interactions discovered to exist between the film components. The importance of film interdiffusion during growth in promoting interactions between film components is found to be critical in the direct incorporation of the weakly charged vancomycin drug in these multilayer films. The resulting coatings are engineered with unprecedented drug densities ranging from 17-220 μg mm(-3) (approximately 20 wt%) for films that are micron to submicron scale in thickness, delivering vancomycin over timescales of 4 h to 2.5 days. The released drug is highly effective in inhibiting Staphylococcus aureus growth in vitro. Taking advantage of the difference in release characteristics between dip and spray assembled films, a composite film architecture was engineered to have both a bolus vancomycin release followed by a period of linear sustained drug release. The control over drug densities and release profiles displayed in this work is necessary to address the requirements of varying medical conditions, including those where immediate infection elimination is needed or long term infection prevention is required.

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